淫羊藿苷介导Nrf2/HO-1信号通路减轻大鼠肾缺血再灌注损伤和氧化应激  

Icariin mediates Nrf2/HO-1 signaling pathway to alleviate renal ischemia reperfusion injury and oxidative stress in rats

作　　者：牟俊杰 冯静[3] 张文松 关欣 陈琴 蒋飞飞 甘措 刘瑶 邓菲[4] Mou Junjie;Feng Jing;Zhang Wensong(School of Clinical Medicine,Southwest Medical University,Luzhou 646000;Dept of Nephrology,Chengdu Jinniu District People's Hospital,Chengdu 610036;Dept of Nephrology,Sichuan Academy of Medical Sciences,Sichuan People's Hospital,Chengdu 610031)

机构地区：[1]西南医科大学临床医学院,泸州646000 [2]成都市金牛区人民医院肾脏内科,成都610036 [3]四川省医学科学院·四川省人民医院肾脏内科,成都610031 [4]四川省医学科学院·四川省人民医院中医科,成都610031

出　　处：《安徽医科大学学报》2021年第3期449-453,457,共6页Acta Universitatis Medicinalis Anhui

基　　金：四川省科技厅科研课题国际合作项目(编号:2019YFH0069);四川省基层卫生事业发展研究中心课题(编号:SWFZ18-Z-6)。

摘　　要：目的探究淫羊藿苷对肾缺血再灌注大鼠病理损伤和氧化应激的影响。方法建立肾缺血再灌注大鼠模型,将大鼠随机分为5组:Control组、RIRI组、RIRI+icariin 25 mg/kg组、RIRI+icariin 50 mg/kg组和RIRI+icariin 100 mg/kg组进行后续实验。试剂盒检测蛋白尿、血清肌酐、尿素氮水平;HE染色检测病理损伤程度;ELISA检测外周血和肾组织中诱导型一氧化氮合酶(iNOS)、白细胞介素-10(IL-10)含量;试剂盒检测超氧化物歧化酶(SOD)、谷胱甘肽(GSH)含量;Western blot检测Caspase-3、Caspase-9、Bax、Bcl-2、Nrf2、p-Nrf2、HO-1蛋白表达水平。结果与Control组比较,RIRI组大鼠蛋白尿、血清肌酐、尿素氮水平升高(P<0.05),呈现明显肾缺血再灌注损伤;cleaved Caspase-3/Caspase-3、cleaved Caspase-9/Caspase-9、Bax/Bcl-2比值升高(P<0.05);外周血和肾组织中iNOS、IL-10含量升高(P<0.05);SOD、GSH含量降低(P<0.05);p-Nrf2/Nrf2比值和HO-1蛋白水平降低(P<0.05)。与RIRI组比较,RIRI+icariin 50、100 mg/kg组大鼠蛋白尿、血清肌酐、尿素氮水平降低(P<0.05),病理损伤程度明显改善,cleaved Caspase-3/Caspase-3、cleaved Caspase-9/Caspase-9、Bax/Bcl-2比值降低(P<0.05),iNOS含量降低(P<0.05),IL-10含量升高(P<0.05),SOD、GSH含量升高(P<0.05)p-Nrf2/Nrf2比值和HO-1蛋白水平升高(P<0.05)。结论淫羊藿苷通过介导Nrf2/HO-1信号通路减轻大鼠肾缺血再灌注损伤和氧化应激。Objective To explore the effect of Icariin on pathological injury and oxidative stress in renal ischemiareperfusion rats.Methods The rat model of renal ischemia-reperfusion was established and the rats were randomly divided into 5 groups:Control group,RIRI group,RIRI+icariin 25 mg/kg group,RIRI+icariin 50 mg/kg group and RIRI+icariin 100 mg/kg group for follow-up experiments.The kit was used to detect the levels of proteinuria,serum creatinine and urea nitrogen.HE staining was used to detect the degree of pathological damage.The contents of iNOS and IL-10 in peripheral blood and kidney tissues were detected by ELISA.The content of SOD and GSH was detected by the kit.Western blot was used to detect the expression levels of Caspase-3,Caspase-9,Bax,Bcl-2,Nrf2,p-Nrf2 and HO-1.Results The results showed that,compared with the Control group,the levels of proteinuria,serum creatinine and urea nitrogen in the RIRI group significantly increased(P<0.05),presenting significant renal ischemia-reperfusion injury,the cleaved Caspase-3/Caspase-3,cleaved Caspase-9/Caspase-9,and Bax/Bcl-2 ratios significantly increased(P<0.05),and the levels of inducible nitric oxide synthase(iNOS)and interleukin-10(IL-10)in the peripheral blood and renal tissues significantly increased(P<0.05).The contents of superoxide dismutase(SOD)and glutathione(GSH)significantly reduced(P<0.05),and the p-Nrf2/Nrf2 ratio and HO-1 protein level significantly reduced(P<0.05).Compared with the RIRI group,the levels of proteinuria,serum creatinine and urea nitrogen in the RIRI+icariin 50 and 100mg/kg groups significantly reduced(P<0.05),and the degree of pathological damage was significantly improved.The ratios of cleaved Caspase-3/Caspase-3,cleaved Caspase-9/Caspase-9 and Bax/Bcl-2 significantly reduced(P<0.05),the iNOS content significantly reduced(P<0.05),and the IL-10 content significantly increased(P<0.05).The contents of SOD and GSH significantly increased(P<0.05).The p-Nrf2/Nrf2 ratio and HO-1 protein level significantly increased(P<0.05).Conclusion Icari

关 键 词：肾缺血再灌注 淫羊藿苷 氧化应激 Nrf2/HO-1信号通路 

分 类 号：R256.5[医药卫生—中医内科学]